TY - JOUR
T1 - Sleep disturbance and kynurenine metabolism in depression
AU - Cho, Hyong Jin
AU - Savitz, Jonathan
AU - Dantzer, Robert
AU - Teague, T. Kent
AU - Drevets, Wayne C.
AU - Irwin, Michael R.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/8
Y1 - 2017/8
N2 - Objective Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound. This relative neurotoxic shift in the balance of kynurenine metabolites has been associated with depression, but never been examined regarding sleep disturbance. We tested the association between sleep disturbance and this relative neurotoxic shift in 68 currently depressed, 26 previously depressed, and 66 never depressed subjects. Methods Sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. Serum concentrations of kynurenine metabolites were measured using high performance liquid chromatography. Putative neuroprotective indices reflecting the relative activity of neuroprotective and neurotoxic kynurenine metabolites were calculated as KynA/QA and KynA/3HK (primary outcomes). Results Sleep disturbance was associated with reduced KynA/QA in the currently depressed group only (unadjusted beta − 0.43, p < 0.001). This association remained significant even after controlling for age, sex, analysis batch, body-mass index, and depressive symptoms in currently depressed subjects (adjusted beta − 0.30, p = 0.02). There was no significant association between sleep disturbance and KynA/3HK in any of the groups. Sleep disturbance was associated with increased C-reactive protein in currently depressed subjects only (unadjusted beta 0.38, p = 0.007; adjusted beta 0.33, p = 0.02). Conclusion These data support the hypothesis that altered kynurenine metabolism may molecularly link sleep disturbance and depression.
AB - Objective Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound. This relative neurotoxic shift in the balance of kynurenine metabolites has been associated with depression, but never been examined regarding sleep disturbance. We tested the association between sleep disturbance and this relative neurotoxic shift in 68 currently depressed, 26 previously depressed, and 66 never depressed subjects. Methods Sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. Serum concentrations of kynurenine metabolites were measured using high performance liquid chromatography. Putative neuroprotective indices reflecting the relative activity of neuroprotective and neurotoxic kynurenine metabolites were calculated as KynA/QA and KynA/3HK (primary outcomes). Results Sleep disturbance was associated with reduced KynA/QA in the currently depressed group only (unadjusted beta − 0.43, p < 0.001). This association remained significant even after controlling for age, sex, analysis batch, body-mass index, and depressive symptoms in currently depressed subjects (adjusted beta − 0.30, p = 0.02). There was no significant association between sleep disturbance and KynA/3HK in any of the groups. Sleep disturbance was associated with increased C-reactive protein in currently depressed subjects only (unadjusted beta 0.38, p = 0.007; adjusted beta 0.33, p = 0.02). Conclusion These data support the hypothesis that altered kynurenine metabolism may molecularly link sleep disturbance and depression.
KW - Depression
KW - Inflammation
KW - Kynurenic acid
KW - Kynurenine pathway
KW - Quinolinic acid
KW - Sleep disturbance
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U2 - 10.1016/j.jpsychores.2017.05.016
DO - 10.1016/j.jpsychores.2017.05.016
M3 - Article
C2 - 28712413
AN - SCOPUS:85019918579
SN - 0022-3999
VL - 99
SP - 1
EP - 7
JO - Journal of Psychosomatic Research
JF - Journal of Psychosomatic Research
ER -